PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Abstract

BACKGROUND Pulmonary hypertension (PH) secondary to left heart failure portends a poor prognosis and is a relative contraindication to heart transplantation at many centers. We tested the hypothesis that when PH persists after adequate left ventricle (LV) unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A (PDE5A) inhibition would decrease PH in this population. METHODS AND RESULTS We performed an open-label clinical trial using control patients not receiving therapy. Between 1999 and 2007, one hundred thirty-eight consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure (PCWP), and PH (defined by a pulmonary vascular resistance (PVR) > 3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their PCWP to a value < 15 mmHg (11.8 +/− 2.0 mmHg from baseline 23.2 +/− 6.2 mmHg) one to two weeks after LVAD implantation, but despite this improvement, the PVR of these patients was only minimally affected (5.65 +/−3.00 to 5.39 +/− 1.78 Wood Units). Twenty-six consecutive patients from this group with persistently elevated PVR were started on oral PDE5A inhibition with sildenafil and titrated to an average of dose of 51.9 mg by mouth three times per day. The average PVR in the sildenafil treated group fell from 5.87 +/− 1.93 to 2.96 +/− 0.92 Wood Units (P<0.001) and the mean pulmonary artery pressure (mPAP) fell from 36.5 +/− 8.6 to 24.3 +/− 3.6mmHg (P<0.0001) and was significantly lower when compared to the thirty-two LVAD recipients not receiving sildenafil at weeks 12–15 after the initial post LVAD hemodynamic measurements (13 to 17 weeks post LVAD implantation). In addition, hemodynamic measurements of right ventricular (RV) function in sildenafil treated patients was also improved compared with patients not receiving sildenafil. CONCLUSIONS In patients with persistent PH after recent LVAD placement, PDE5A inhibition in this open label trial resulted in a significant decrease in PVR as compared with control patients.

Predictors and Management of Right Heart Failure after Left Ventricular Assist Device Implantation

“…25,26 Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor commonly used as a selective vasodilator and can lower PVR in persistent pulmonary hypertension post-LVAD implant. 27 …”

Treatment of Secondary Pulmonary Hypertension with Bosentan after Left Ventricular Assist Device Implantation

“…Although some studies have demonstrated a decrease in PVR after LVAD [7,8,26], the majority of this literature comes from retrospective, single center data that either included patients on pulmonary vasodilator therapy or did not describe whether such therapy was used. There are also data from a prospective study by Tedford et al [9] that indicates some patients with persistent PH after LVAD insertion do not experience a decrease in PVR over time despite LV unloading. Ultimately, it remains unclear whether pulmonary vasodilator therapy provides a significant benefit to patients with elevated PVR and/or RV dysfunction.…”

“…However, many patients will have a persistently elevated PVR despite left-sided mechanical support [9]. Moreover, those with persistent PH and RV dysfunction are at increased risk of adverse complications, including death, following the initiation of LVAD support [10,11].…”

“…These observations have led to an interest in using pulmonary vasodilators as adjunctive therapy for patients with RV dysfunction after LVAD implant. Small studies of the phosphodiesterase V inhibitor, sildenafil, have provided evidence that pulmonary vasodilators may further improve pulmonary vascular hemodynamics in LVAD patients [9,12]. As a consequence, many patients on mechanical support are treated with pulmonary vasodilators; however, the benefits of this practice remain unclear.…”

Mechanical Circulatory Support for Advanced Heart Failure

“…[52][53][54][55] If pulmonary vascular resistance remains elevated, sildenafil may be considered. 56 Other contraindications to transplant such as severe chronic kidney disease or morbid obesity seldom improve to a degree that allows listing. Given the scarcity of donor organs and improving outcomes with LVAD support, recipients who are not transplant candidates at time of implant should be prepared for the possibility of lifetime mechanical support.…”